Iron supplementation in previously anemic Bolivian children normalized hematologic parameters, but not immunologic parameters.

Iron deficiency anemia (IDA) is considered to be the most prevalent micronutrient deficiency in the world. Estimates indicate that 1.2 billion people suffer mild to severe forms of anemia and that up to 46% of schoolchildren in developing countries are affected. In 2003, ENDSA, the national demographic and health survey of Bolivia showed that 60% of children under five and 72% of children under 2 years old were anemic. Micronutrient deficiency has been suggested to impair cell-mediated immunity. In particular, iron, zinc and vitamin A deficiencies have an impact on the immune system. In vitro and in vivo laboratory studies indicate a link between iron deficiency and impaired T-lymphocyte proliferation. The exact effects or mechanisms of iron deficiency on maturation and proliferation of T-lymphocytes in vivo are, however, not yet known. This study investigated the effects of iron on the maturation of T-lymphocytes in anemic but otherwise healthy schoolchildren (no apparent protein-energy deficiency or other morbidity). Anemic children of a poor peri-urban school of Cochabamba city, Bolivia, were given iron treatment for three consecutive months. We chose to look at CD1a+ lymphocytes, which are immature thymocytes. The proportions of CD1a+ lymphocytes in the peripheral circulation measured at baseline and after treatment were compared with a reference group of age-matched non-anemic children controls from the same school. The immunologic parameters, although improved, did not reach the proportions of the control group. Overall, the proportion of circulating immature T-lymphocytes decreased from 18.3% to 9.2% in the treated following iron supplementation in anemic children, compared with 3.4% in non-anemic children.

["CLAPSEN", a global approach to the rehabilitation of severe childhood malnutrition in Bolivia]. / Le <>, une démarche globale pour la réhabilitation nutritionnelle de l'enfant gravement mal nourri en Bolivie.

The "CLAPSEN" approach was developed at the Hospital Materno Infantil German Urquidi in Cochabamba, to provide a global response for the study and treatment of childhood malnutrition. "CLAPSEN" is short for Clinical, Laboratory, Anthropometry, Psychology, Sociology, Nursing (Enfermera in Spanish) and Nutritional care. Most of the malnourished children admitted to Cochabamba Hospital are from poor families, more than three quarters of whom have only recently arrived in the city. Acute malnutrition is just one of the manifestations of a generally unfavorable environment. Malnutrition should not be considered as a simple deficiency in energy, protein or micronutrients, but rather as a multi-deficiency syndrome, also involving a lack of basic health and social care. This study demonstrates that malnourished children display a considerable degree of psychological retardation and of immune system depression. After five weeks of rehabilitation, the children were considered to have recuperated physically, as assessed by anthropometry, but not psychologically, as assessed by the adapted Dewer Score, or immunologically, as shown by the size of the thymus or the extent of maturation of lymphocytes. This strategy was not designed as a long-term approach for treating malnutrition, but rather as a research project to characterize the children arriving at the hospital, to determine the reasons for their malnutrition and to identify strategies that could be implemented earlier by health centers of social services, to prevent deterioration in the condition of these children to severe malnutrition requiring hospital admission. We believe that, in this Latin American context, in which the rate of acute malnutrition is low, the hospital should continue to be involved in the treatment of severely malnourished children with associated diseases. The child's stay in hospital should be short and once the child has recovered clinically, he should be sent home. In light of the observed levels of social deprivation, psychosocial and immune deficits, there appears to be a need for continued support for the family, to ensure the full recovery of the child and to prevent relapses.

Immune recovery of malnourished children takes longer than nutritional recovery: implications for treatment and discharge.

Protein-energy malnutrition decreases cellular immunity yet immune recovery has rarely been investigated during nutritional rehabilitation. Malnourished children from low income families of Cochabamba (Bolivia) were hospitalized for 2 months in the Center for Immune and Nutritional Rehabilitation (CRIN), of the German Urquidi Materno-Infantil Hospital. They received a special four-step diet. Nutritional status was determined by a daily clinical examination and weekly anthropometric measurements. Immune status was assessed by weekly ultrasonography of the thymus. The classical criterion for discharge (90 per cent of median reference weight for height) was reached after the first month, whereas a 2-month period was required for complete immunologic recovery. The children belonged to disadvantaged population groups with high exposure to disease. In such an environment, discharge based only on nutritional status after 1 month of treatment could explain frequent relapses because the children were still immunodepressed.

[Immuno-nutritional recovery of children with severe malnutrition]. / Réhabilitation immunonutritionnelle d'enfants atteints de malnutrition sévère.

In developing countries, more than 12 million children die each year from the combined effects of malnutrition and infection. Malnourished children have impaired cellular immunity and are particularly sensitive to opportunistic infections. However, immune recovery has rarely been investigated during nutritional rehabilitation. Indeed, mortality remains high during renutrition, and relapses are frequent. We established a center in Cochabamba, Bolivia, specifically to save these children by treating both clinical and nutritional problems and restoring immune function. The CRIN (center for immuno-nutritional recovery) admits children with severe malnutrition from the Cochabamba suburban area. They are from low income families, in crowded living conditions with poor sanitation and are weaned early. Nutritional diagnosis was based on weight-for-height, arm to head circumference ratio and clinical examination for edema, loss of subcutaneous tissue and diminished muscle mass. The children were examined daily, and first treated for respiratory and intestinal infections. Sociological and psychological aspects were also included in our holistic approach to treating severe malnutrition. Children received a four-stage diet lasting 2 months. During the initial phase (1 week) they were given an oil-sugar-milk based diet, with half lactose concentration, seven times a day. This supplied 1.5 to 2.5 g of protein and 120 to 150 kcal/kg of body weight, according to the PEM pattern. Protein and energy intake was then slowly increased during the transition phase (1 week). During the next, 'calorific-protein bombing' phase (6 weeks) 5 g of protein and 200 kcal/kg of body weight were given daily, such that there was sufficient energy for protein accumulation. During the last, discharge phase (1 week), the protein and energy contents were slowly decreased. Weight, height, arm and head circumferences, and triceps skin-fold thickness were measured weekly by standardized methods. Thymus size was assessed weekly by mediastinal ultrasound scanning with a portable scanner (ALOKA SSD-210 DXII, Tokyo) using a 5 MHz linear pediatric probe. Lymphocyte subpopulations in peripheral blood were investigated monthly using monoclonal antibodies. Compared to controls, the malnourished group had severe involution of the thymus, a significantly higher proportion of circulating immature T lymphocytes and a lower proportion of mature T lymphocytes. The two month longitudinal study showed that normal anthropometric values (90% NCHS weight for height) were recovered after one month of rehabilitation. However, immune recovery (thymic area of 350 nm2) required two months. This may explain the frequent relapses among malnourished children discharged after one month on the basis of 'apparent nutritional health'. Such children may remain immunodepressed, and should therefore be considered as high risk children. To test an immunostimulatory treatment, we designed a historical cohort study of malnourished children who received 2 mg of zinc per day. The children were matched for age, sex, anthropometric criteria and nutritional status with malnourished control children (treated previously with zinc). Anthropometric recovery was obtained in both groups in one month. Children receiving zinc attained immunological recovery within one month, whereas children not receiving zinc took two months. Thus zinc hastened immunological recovery concomitant with nutritional recovery such that the duration of hospitalization could be halved: after one month of this immuno-nutritional treatment, malnourished children appear to be sufficiently healthy to face their pathogenic home environment.